AYVAKIT is the FIRST and ONLY therapy approved
for indolent systemic mastocytosis (ISM)1
Designed for potent and selective inhibition of KIT D816V1
AYVAKIT demonstrated statistically significant improvements vs placebo for primary and key secondary efficacy endpoints in the PIONEER study1
Study Design
PIONEER (N=212) was a phase 2, multipart, randomized, placebo-controlled, double-blind study evaluating the efficacy and safety of AYVAKIT 25 mg + best supportive care (BSC) (n=141) vs placebo + BSC (n=71) over 24 weeks in adult patients (≥18 years) with a centrally confirmed ISM diagnosis per WHO criteria, and with moderate to severe ISM despite receiving at least 2 symptom-directed therapies. Patients were randomized 2:1 to receive AYVAKIT 25 mg + BSC or placebo + BSC. Patients who completed the 24-week double-blind portion of the trial had the option to enter an open-label extension treatment period for up to 5 years and receive AYVAKIT 25 mg + BSC.1,2
- Primary endpoint: Absolute mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) total symptom score (TSS) compared with placebo + BSC from baseline to Week 241
- Select key secondary endpoints: Proportion of patients achieving ≥50% reduction in serum tryptase levels; ≥50% reduction in KIT D816V VAF or undetectable; ≥50% reduction in bone marrow mast cells or no aggregates, all compared with placebo + BSC at Week 241
SELECT BASELINE DEMOGRAPHIC AND DISEASE CHARACTERISTICS (N=212)1,2
- 93% of patients in the AYVAKIT + BSC arm had a KIT D816V mutation1
- BSC medications allowed in the PIONEER study included anti-immunoglobulin E antibody (omalizumab), glucocorticoids, cromolyn sodium, H1 antihistamines, H2 antihistamines, leukotriene inhibitors, and proton pump inhibitors2
- Key eligibility criteria: ≥18 years of age; centrally confirmed ISM diagnosis per WHO criteria; uncontrolled moderate to severe ISM symptoms, defined as ISM-SAF TSS ≥28, despite ≥2 classes of symptom-directed therapies2
ITT analysis: Markov chain Monte Carlo simulation was used to impute the missing values at Baseline or Week 24.
ISM-SAF TSS OVER TIME2
ITT analysis: Markov chain Monte Carlo simulation was used to impute the missing values.
LIMITATIONS: Mean change in TSS at all time points except Week 24 were prespecified, nonranked endpoints and were not adjusted for multiplicity. Therefore, treatment differences at these time points cannot be regarded as statistically significant and results should be interpreted with caution.
PROPORTION OF PATIENTS ACHIEVING ≥50%
REDUCTION IN OBJECTIVE MEASURES OF MAST CELL BURDEN AT 24 WEEKS1
52.8% of 106 patients receiving AYVAKIT + BSC achieved ≥50% reduction in BM MCs vs 22.8% of 57 patients receiving placebo + BSC (2-sided P<0.0001)1‡
ITT analysis: For patients with high-dose steroid use within 7 days before Week 24, or greater than 14 consecutive days at any point from baseline to Week 24, the Week 24 score was set to missing.
Patients received BSC and either AYVAKIT or placebo.
†Percent of patients with ≥50% reduction in peripheral blood KIT D816V VAF or undetectable.
‡Percent of patients with ≥50% reduction in BM MCs or no aggregates.
AYVAKIT demonstrated a significant improvement in ISM-SAF TSS at 24 weeks1
Patients received BSC and either AYVAKIT or placebo1
ITT analysis: Markov chain Monte Carlo simulation was used to impute the missing values at Baseline or Week 24.
ISM-SAF TSS OVER TIME2
ITT analysis: Markov chain Monte Carlo simulation was used to impute the missing values.
LIMITATIONS: Mean change in TSS at all time points except Week 24 were prespecified, nonranked endpoints and were not adjusted for multiplicity. Therefore, treatment differences at these time points cannot be regarded as statistically significant and results should be interpreted with caution.
*The Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) is a patient-reported outcome tool assessing 11 ISM signs and symptoms: abdominal pain, nausea, diarrhea, spots, itching, flushing, bone pain, fatigue, dizziness, headache, brain fog. Scores ranged from 0 (“none”) to 10 (“worst imaginable”). The item scores were summed to calculate a daily ISM-SAF TSS (range 0-110), with higher scores indicating greater symptom severity. A biweekly average ISM-SAF TSS was used to evaluate efficacy endpoints.1
Significantly more patients treated with AYVAKIT had reductions in objective measures of mast cell burden at 24 weeks1
PROPORTION OF PATIENTS ACHIEVING ≥50% REDUCTION IN OBJECTIVE MEASURES OF MAST CELL BURDEN AT 24 WEEKS1
52.8% of 106 patients receiving AYVAKIT + BSC achieved ≥50% reduction in BM MCs vs 22.8% of 57 patients receiving placebo + BSC (2-sided P<0.0001)1‡
ITT analysis: For patients with high-dose steroid use within 7 days before Week 24, or greater than 14 consecutive days at any point from baseline to Week 24, the Week 24 score was set to missing.
Patients received BSC and either AYVAKIT or placebo.
†Percent of patients with ≥50% reduction in peripheral blood KIT D816V VAF or undetectable.
‡Percent of patients with ≥50% reduction in BM MCs or no aggregates.
ADVERSE REACTIONS OCCURRING IN PATIENTS WITH ISM DURING PIONEER TRIAL1
aAdverse reactions that occurred in ≥5% of AYVAKIT-treated patients and ≥2% more than placebo-treated patients.
bPer National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
cEye edema includes periorbital edema, eye edema, swelling of eyelid, orbital edema, eye swelling, eyelid edema and eyelid ptosis.
dTerm includes several similar terms.
eRespiratory tract infection includes pneumonia, upper respiratory tract infection, bronchitis and respiratory tract infection.
fHematoma includes contusion, hematoma and pelvic hematoma.
gHemorrhage includes epistaxis, gingival bleeding, hematochezia, rectal hemorrhage, retinal hemorrhage.
- Serious adverse reactions occurred in 1 patient (0.7%) who received AYVAKIT due to pelvic hematoma1
- Permanent discontinuation of AYVAKIT due to an adverse reaction occurred in 1 patient (0.7%) due to dyspnea and dizziness1
- Dosage interruptions of AYVAKIT due to an adverse reaction occurred in 5% of patients1
- Of all adverse reactions, 55% were Grade 1, 38% were Grade 2, and 7% were Grade 31
- Among patients with edema adverse reactions, 95% were Grade 1 and 5% were Grade 2. Among patients with hemorrhage adverse reactions, 86% were Grade 1 and 14% were Grade 21
The recommended dosage of AYVAKIT for patients with
ISM is 25 mg orally, once daily1
One 25-mg
tablet orally
On an empty stomach,
at least 1 hour before
or at least 2 hours after a meal
Once a day
A modified starting dosage of AYVAKIT is recommended for patients with severe hepatic impairment (Child-Pugh Class C): 25 mg orally every other day.1
Avoid concomitant use of AYVAKIT with strong or moderate CYP3A inhibitors or inducers.1
INDICATION
INDICATION & IMPORTANT SAFETY INFORMATION
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).
Limitations of Use: AYVAKIT is not recommended for patients with platelet counts of <50 x 109/L.
INDICATION
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).
Limitations of Use: AYVAKIT is not recommended for patients with platelet counts of <50 x 109/L.
IMPORTANT SAFETY INFORMATION
Intracranial Hemorrhage (ICH)—Serious ICH may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. No events of ICH occurred in the 246 patients with ISM who received any dose of AYVAKIT in the PIONEER study.
Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia.
Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH.
Permanently discontinue AYVAKIT if ICH of any grade occurs.
Cognitive Effects—Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 7.8% of patients with ISM who received AYVAKIT + best supportive care (BSC) versus 7.0% of patients who received placebo + BSC; <1% were Grade 3. Depending on the severity, withhold AYVAKIT and then resume at the same dose, or permanently discontinue AYVAKIT.
Photosensitivity—AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.
Embryo-Fetal Toxicity—AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
Adverse Reactions—The most common adverse reactions (≥10%) in patients with ISM were eye edema, dizziness, peripheral edema, and flushing.
Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors or inducers.
To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click here to see the full Prescribing Information for AYVAKIT.
References:
- AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; May 2023.
- Gotlib J et al. NEJM Evid 2023. Available online. doi:10.1056/EVIDoa2200339
INDICATION
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).
Limitations of Use: AYVAKIT is not recommended for patients with platelet counts of <50 x 109/L.
INDICATION
INDICATION & IMPORTANT SAFETY INFORMATION
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).
Limitations of Use: AYVAKIT is not recommended for patients with platelet counts of <50 x 109/L.
INDICATION
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).
Limitations of Use: AYVAKIT is not recommended for patients with platelet counts of <50 x 109/L.
IMPORTANT SAFETY INFORMATION
Intracranial Hemorrhage (ICH)—Serious ICH may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. No events of ICH occurred in the 246 patients with ISM who received any dose of AYVAKIT in the PIONEER study.
Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia.
Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH.
Permanently discontinue AYVAKIT if ICH of any grade occurs.
Cognitive Effects—Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 7.8% of patients with ISM who received AYVAKIT + best supportive care (BSC) versus 7.0% of patients who received placebo + BSC; <1% were Grade 3. Depending on the severity, withhold AYVAKIT and then resume at the same dose, or permanently discontinue AYVAKIT.
Photosensitivity—AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.
Embryo-Fetal Toxicity—AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
Adverse Reactions—The most common adverse reactions (≥10%) in patients with ISM were eye edema, dizziness, peripheral edema, and flushing.
Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors or inducers.
To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click here to see the full Prescribing Information for AYVAKIT.
References:
- AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; May 2023.
- Gotlib J et al. NEJM Evid 2023. Available online. doi:10.1056/EVIDoa2200339
INDICATION
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).
Limitations of Use: AYVAKIT is not recommended for patients with platelet counts of <50 x 109/L.
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05/2023 USBP-PRAVAISM-23.048.1